Abstract
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex. AP1 regulates the size but not the composition of SVP transport carriers. Additionally, UNC-16 and LRK-1 through the AP-3 complex regulates the composition but not the size of the SVP transport carrier. These early biogenesis steps are essential for dependence on the synaptic vesicle motor, UNC-104 for axonal transport. Our results show that UNC-16 and its downstream effectors, LRK-1 and the AP complexes function at the Golgi and/or post-Golgi compartments to control early steps of SV biogenesis. The UNC-16 dependent steps of exclusion, inclusion and motor recruitment are critical for polarized distribution of neuronal cargo.
Highlights
The secretory pathway in a cell involves the synthesis and trafficking of proteins through the ER-Golgi network and their subsequent targeting to different sub-cellular compartments
We show that UNC-16/ JIP3 plays a critical role, in a series of essential steps, to ensure proper membrane composition and size of the ensuing synaptic vesicle proteins (SVPs) carrier exiting the cell body
We show that the UNC-16 through LRK-1 and the adaptor protein (AP)-3 complex ensures that specific SVPs are included in the same transport carrier
Summary
The secretory pathway in a cell involves the synthesis and trafficking of proteins through the ER-Golgi network and their subsequent targeting to different sub-cellular compartments. Generation of a defined transport carrier, with a characteristic protein and lipid composition, along the trafficking pathways is known to involve at least three steps (a-c, see below), several occurring at the trans-Golgi network (TGN). AP-1 interacts with the Kinesin-3 motor KIF13A to coordinate endosomal sorting during melanosome biogenesis [11] These events ensure the formation of a defined transport carrier that gets targeted to a specific sub-cellular compartment. During the multi-step maturation of secretory granules, sorting of proteins occur post-Golgi at intermediate compartments known as the immature secretory granules (ISGs) [12]. The genes that regulate such processes remain to be well understood
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